Anemia in pregnancy

Anemia in pregnancy is a decrease in the total red blood cells (RBCs) or hemoglobin in the blood during pregnancy or in the period following pregnancy. It involves a reduction in the oxygen carrying capacity of the blood. Anemia is an extremely common condition in pregnancy and postpartum world-wide, conferring a number of health risks to mother and child.[1] Maternal signs and symptoms are usually non-specific, but can include: fatigue, pallor, dyspnea, palpitations and dizziness. There are numerous well-known maternal consequences of anemia including: maternal cardiovascular strain, reduced physical and mental performance, reduced peripartum blood reserves, increased risk for peripartum blood product transfusion, and increased risk for maternal mortality.[2]

Signs and symptoms

Symptoms may be mild such as fatigue and pallor or more severe, such as fainting or difficulty breathing.[3]

Causes

In the simplest of terms, anemia results from impaired production of red blood cells, increased destruction of red blood cells or blood loss.[4] Anemia can be congenital (ie, conditions such as sickle cell anemia and thalassemia) or acquired (ie, conditions such as iron deficiency anemia or anemia as a result of an infection).

The most frequent cause of anemia in pregnancy worldwide is iron deficiency anemia (IDA).[1][5] Iron is needed for many physiological processes in the body, and observational studies indicate that iron deficiency during pregnancy may independently result in cognitive or behavioral abnormalities in the child.[6] Babies of women with IDA have an increased risk of being low birthweight, being born prematurely, being more susceptible to infections, and suffering death in utero.[2][5]

Aside from iron deficiency, other causes of anemia in the peripartum woman include nutritional deficits such as folate and vitamin B12 deficiencies. Congenital causes of anemia that may worsen during pregnancy include: hemoglobinopathies, such as sickle cell anemia and thalassemia, as well as conditions of red cell structural and enzymatic abnormalities such as hereditary spherocytosis and elliptocytosis. Bacterial, viral, fungal, and protozoal infections (such as malaria and hookworm) may also result in anemia. Hemolytic anemia, aplastic anemia and anemia due to hematologic or non-hematologic  (ie, colonic adenocarcinoma) malignancy may rarely occur during pregnancy as well. Peri and postpartum hemorrhage may induce or worsen pre-existing anemia in the postpartum woman.

Prevention and treatment, especially of iron deficiency anemia, is widely available, but not consistently performed. Severe anemia may require red blood cell transfusions especially if there is also significant blood loss at birth.

  • Maternal deficiency of iron is by far the most common cause of obstetric anemia and is a treatable condition
  • Maternal anemia is frequent despite guidelines and widely available treatment
  • Maternal anemia is thought to be the most frequent cause of maternal death worldwide
  • Anemia during pregnancy increases the risk of induction of labor and cesarean section
  • Anemia during pregnancy increases the risk of postpartum anemia
  • Iron deficiency during pregnancy is linked to a number of harmful effects on the fetus such as intrauterine growth restriction, death in utero, infection, preterm delivery and neurodevelopmental damage, which may be irreversible[6][7][8]
  • Failure to treat maternal iron deficiency may carry over to a woman's next pregnancy

Iron deficiency is the most common cause of anemia in the pregnant woman. During pregnancy, the average total iron requirement is about 1200 mg per day for a 55 kg woman. This iron is used for the increase in red cell mass, placental needs and fetal growth.[2] About 40% of women start their pregnancy with low to absent iron stores and up to 90% have iron stores insufficient to meet the increased iron requirements during pregnancy and the postpartum period.[2]

Deficiencies of folate and vitamin B12 can lead to anemia in the pregnant patient. Parasitic infestations with hookworm or Plasmodium species may also result in anemia. Other infectious causes include: bacterial, fungal and viral infections. Congenital anemias such as sickle cell anemia and thalassemia may worsen during pregnancy due to increased demands. Even less common causes include hemolytic anemia, aplastic anemia, and hematologic malignancies in the pregnant woman.

The majority of women presenting with postpartum anemia have pre-delivery iron deficiency anemia or iron deficiency anemia combined with acute blood loss during delivery.[9]

Postpartum bleeding

Postpartum hemorrhage is typically defined as blood loss in excess of 500 mL following vaginal delivery and in excess of 1000 mL following cesarean delivery.[10] Primary PPH is that which occurs within 24 hours after delivery, while secondary PPH can occur up to 12 weeks following delivery. PPH is relatively common with an incidence of 5–15% of all births. However, life-threatening PPH, defined by the Royal College of Obstetricians and Gynaecologists (RCOG) as an estimated blood loss in excess of 2500 mL or receipt of > 5 units of blood products or treatment of coagulopathy, occurs in an estimated 3.7 per 1000 pregnancies. [10]

Diagnosis

The most useful test with which to render a diagnosis of anemia is a low RBC count,[3] however hemoglobin and hematocrit values are most commonly used in making the initial diagnosis of anemia. It is important to note that references ranges for these values are often not the same for pregnant women. Additionally, laboratory values for pregnancy often change throughout the duration of a woman’s gestation.[11]

Testing involved in diagnosing anemia in the pregnant woman must be tailored to each individual patient. Suggested tests include: hemoglobin and hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), erythrocyte count, red cell distribution width (RDW), reticulocyte count, and a peripheral smear to assess red blood cell morphology. If iron deficiency is suspected, additional tests such as: serum iron, total iron-binding capacity (TIBC), transferrin saturation, and plasma or serum ferritin may be warranted.

Hemoglobin < 10 g/dL in the postpartum woman is classified as anemia.

Pregnancy

Hormonal changes in the pregnant woman result in an increase in circulating blood volume to 100 mL/kg with a total blood volume of approximately 6000–7000 mL. While red cell mass increases by 15–20% during pregnancy, plasma volume increases by 40%.[12]

Hemoglobin levels less than 11 g/dL during the first trimester, less than 10.5 g/dL during the second and third trimesters and less than 10 mg/dL in the postpartum period are considered anemic.[5]

Prevention

Iron deficiency anemia can be prevented by taking 15–60 mg of iron orally daily.[13]

Treating anemia during pregnancy and managing obstetric hemorrhage reduces the incidence of iron deficiency anemia.

Treatment

For treatment of pregnant woman with iron deficiency anemia, doses of oral elemental iron between 65–200 mg per day are recommended. While oral iron is presently the gold standard for mild to moderate iron-deficiency anemia,[2] treatment doses of elemental iron often result in significant gastrointestinal side effects, resulting in reduced compliance. If oral iron cannot be tolerated or is proven ineffective, intravenous iron can induce repletion of iron stores within 1–2 days and normalization of hemoglobin levels in 1–3 weeks.[1][2]

Treatment should target the underlying disease or condition affecting the patient.

  • The majority of obstetric anemia cases can be treated based on their etiology if diagnosed in time. Oral iron supplementation is the gold standard for the treatment of iron deficiency anemia and intravenous iron can be used when oral iron is not effective or tolerated from the second trimester of pregnancy onwards.[14]
  • Treatment of postpartum hemorrhage is multifactorial and includes medical management, surgical management along with blood product support.[10] [15]

Transfusion

Blood product transfusion carries a number of risks both infectious as well as non-infectious. Transfusion transmissible diseases include, but are not limited to the following: human immunodeficiency virus (HIV), hepatitis C virus, hepatitis B virus, West Nile virus, syphilis, Chagas disease, Zika virus, Dengue fever and Chikungunya virus. Non-infectious risks of blood product transfusion include, but are not limited to: hemolytic transfusion reactions, allergic and anaphylactic transfusion reactions, transfusion associated circulatory overload, transfusion related acute lung injury, transfusion associated graft versus host disease and febrile non-hemolytic transfusion reactions. Because of these risks, blood product transfusion should only be used in cases of acute bleeding, severe cases of refractory anemia and in conditions where maternal hemoglobin levels are so low, that there is thought to be imminent risk to mother or fetus.

Epidemiology

In healthy women after normal delivery, the prevalence of anemia (defined as hemoglobin < 11 g/dL) 1 week postpartum is 14% in iron supplemented women and 24% in non-supplemented women.[9]

Guidelines
  1. Pavord S, Myers B, Robinson S, Allard S, Strong J, Oppenheimer C on behalf of the British Committee for Standards in Haematology. UK guidelines on the management of iron deficiency in pregnancy. Br J Haematol. 2012 Mar;156(5):588-600. PMID 2251200
  2. Markova V, Norgaard A, Jorgensen KJ, Langhoff-Roos J. Treatment for women with postpartum iron deficiency anaemia. Cochrane Database Syst Rev. 2015 Aug 13;(8):CD010861. PMID 26270434
  3. Pena-Rosas JP, De-Regil LM, Dowswell T, Viteri FE. Daily oral iron supplementation during pregnancy. Cochrane Database Syst Rev. 2012 Dec 12;12:CD004736. PMID 23235616
  4. Dahlke JD, Mendez-Figueroa H, Maggio L, Hauspurg AK, Sperling JD, Chauhan SP, Rouse DJ. Prevention and management of postpartum hemorrhage: a comparison of 4 national guidelines. Am J Obstet Gynecol. 2015 Jul; 213(1):76e1-10. PMID 25731692
  5. Shaylor R, Weiniger CF, Austin N, Tzabazis A, Shander A, Goodnough LT, Butwick AJ. National and international guidelines for patient blood management in obstetrics: a qualitative review. Anesth Analg 2017;124:216-32. PMID 27557476
  6. Tunçalp Ő, Souza JP, Gűlmezoglu M. New WHO recommendations on prevention and treatment of postpartum hemorrhage. Int J Gynaecol Obstet. 2013 Dec;123(3):254-6. PMID 24054054

References
  1. Pavord, Sue; Myers, Bethan; Robinson, Susan; Allard, Shubha; Strong, Jane; Oppenheimer, Christina; British Committee for Standards in Haematology (March 2012). "UK guidelines on the management of iron deficiency in pregnancy". British Journal of Haematology. 156 (5): 588–600. doi:10.1111/j.1365-2141.2011.09012.x. ISSN 1365-2141. PMID 22512001.
  2. Breymann, Christian (October 2015). "Iron Deficiency Anemia in Pregnancy". Seminars in Hematology. 52 (4): 339–347. doi:10.1053/j.seminhematol.2015.07.003. ISSN 1532-8686. PMID 26404445.
  3. Henry's clinical diagnosis and management by laboratory methods. Henry, John Bernard, 1928-2009., McPherson, Richard A., Pincus, Matthew R. (22nd ed.). Philadelphia, PA: Elsevier/Saunders. 2011. ISBN 9781437709742. OCLC 700376882.CS1 maint: others (link)
  4. "Home | National Heart, Lung, and Blood Institute (NHLBI)". www.nhlbi.nih.gov. Retrieved 2018-07-25.
  5. Roy, N. B. A.; Pavord, S. (April 2018). "The management of anaemia and haematinic deficiencies in pregnancy and post-partum". Transfusion Medicine (Oxford, England). 28 (2): 107–116. doi:10.1111/tme.12532. ISSN 1365-3148. PMID 29744977.
  6. Geng, Fengji; Mai, Xiaoqin; Zhan, Jianying; Xu, Lin; Zhao, Zhengyan; Georgieff, Michael; Shao, Jie; Lozoff, Betsy (December 2015). "Impact of Fetal-Neonatal Iron Deficiency on Recognition Memory at 2 Months of Age". The Journal of Pediatrics. 167 (6): 1226–1232. doi:10.1016/j.jpeds.2015.08.035. ISSN 1097-6833. PMC 4662910. PMID 26382625.
  7. Beard, John L. (December 2008). "Why iron deficiency is important in infant development". The Journal of Nutrition. 138 (12): 2534–2536. doi:10.1093/jn/138.12.2534. ISSN 1541-6100. PMC 3415871. PMID 19022985.
  8. Lozoff, Betsy; Beard, John; Connor, James; Barbara, Felt; Georgieff, Michael; Schallert, Timothy (May 2006). "Long-lasting neural and behavioral effects of iron deficiency in infancy". Nutrition Reviews. 64 (5 Pt 2): S34–43, discussion S72–91. doi:10.1301/nr.2006.may.S34-S43. ISSN 0029-6643. PMC 1540447. PMID 16770951.
  9. Milman, Nils (November 2011). "Postpartum anemia I: definition, prevalence, causes, and consequences". Annals of Hematology. 90 (11): 1247–1253. doi:10.1007/s00277-011-1279-z. ISSN 1432-0584. PMID 21710167.
  10. Dahlke, Joshua D.; Mendez-Figueroa, Hector; Maggio, Lindsay; Hauspurg, Alisse K.; Sperling, Jeffrey D.; Chauhan, Suneet P.; Rouse, Dwight J. (July 2015). "Prevention and management of postpartum hemorrhage: a comparison of 4 national guidelines". American Journal of Obstetrics and Gynecology. 213 (1): 76.e1–10. doi:10.1016/j.ajog.2015.02.023. ISSN 1097-6868. PMID 25731692.
  11. Abbassi-Ghanavati, Mina; Greer, Laura G.; Cunningham, F. Gary (December 2009). "Pregnancy and laboratory studies: a reference table for clinicians". Obstetrics and Gynecology. 114 (6): 1326–1331. doi:10.1097/AOG.0b013e3181c2bde8. ISSN 1873-233X. PMID 19935037.
  12. Jansen, A. J. G.; van Rhenen, D. J.; Steegers, E. a. P.; Duvekot, J. J. (October 2005). "Postpartum hemorrhage and transfusion of blood and blood components". Obstetrical & Gynecological Survey. 60 (10): 663–671. doi:10.1097/01.ogx.0000180909.31293.cf. ISSN 0029-7828. PMID 16186783.
  13. Peña-Rosas, Juan Pablo; De-Regil, Luz Maria; Garcia-Casal, Maria N.; Dowswell, Therese (2015-07-22). "Daily oral iron supplementation during pregnancy". The Cochrane Database of Systematic Reviews (7): CD004736. doi:10.1002/14651858.CD004736.pub5. ISSN 1469-493X. PMID 26198451.
  14. Markova, Veronika; Norgaard, Astrid; Jørgensen, Karsten Juhl; Langhoff-Roos, Jens (2015-08-13). "Treatment for women with postpartum iron deficiency anaemia". The Cochrane Database of Systematic Reviews (8): CD010861. doi:10.1002/14651858.CD010861.pub2. ISSN 1469-493X. PMID 26270434.
  15. Shaylor, Ruth; Weiniger, Carolyn F.; Austin, Naola; Tzabazis, Alexander; Shander, Aryeh; Goodnough, Lawrence T.; Butwick, Alexander J. (January 2017). "National and International Guidelines for Patient Blood Management in Obstetrics: A Qualitative Review". Anesthesia and Analgesia. 124 (1): 216–232. doi:10.1213/ANE.0000000000001473. ISSN 1526-7598. PMC 5161642. PMID 27557476.
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